Effect of Altered Redox States on Expression and DNA-Binding Activity of Hypoxia-Inducible Factor 1

1995 ◽  
Vol 212 (2) ◽  
pp. 550-556 ◽  
Author(s):  
G.L. Wang ◽  
B.H. Jiang ◽  
G.L. Semenza
Keyword(s):  
Dna Binding ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Redox States ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity

scholarly journals Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension

1996 ◽  
Vol 271 (4) ◽  
pp. C1172-C1180 ◽  
Author(s):  
B. H. Jiang ◽  
G. L. Semenza ◽  
C. Bauer ◽  
H. H. Marti
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Functional Characterization ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Maximal Response ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein implicated in the transcriptional activation of genes encoding erythropoietin, glycolytic enzymes, and vascular endothelial growth factor in hypoxic mammalian cells. In this study, we have quantitated HIF-1 DNA-binding activity and protein levels of the HIF-1 alpha and HIF-1 beta subunits in human HeLa cells exposed to O2 concentrations ranging from 0 to 20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and cellular O2 consumption. HIF-1 DNA-binding activity, HIF-1 alpha protein and HIF-1 beta protein each increased exponentially as cells were subjected to decreasing O2 concentrations, with a half maximal response between 1.5 and 2% O2 and a maximal response at 0.5% O2, both in the presence and absence of KCN. The HIF-1 response was greatest over O2 concentrations associated with ischemic/hypoxic events in vivo. These results provide evidence for the involvement of HIF-1 in O2 homeostasis and represent a functional characterization of the putative O2 sensor that initiates hypoxia signal transduction leading to HIF-1 expression.

scholarly journals Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3610-3615 ◽  
Author(s):  
GL Wang ◽  
GL Semenza
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Cobalt Chloride ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Ferrous Ammonium Sulfate ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Hep3b Cells

Abstract Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia- inducible factor 1 (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the EPO gene at a site that is required for transcriptional activation. HIF-1 DNA-binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. DFX appears to induce HIF-1 by chelating iron as induction was inhibited by coadministration of ferrous ammonium sulfate. DFX administration to mice transiently increased EPO RNA levels in the kidney. As previously shown for hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO-producing cells, suggesting the existence of a common hypoxia signal-transduction pathway leading to HIF-1 induction in different cell types.

scholarly journals Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3610-3615 ◽  
Author(s):  
GL Wang ◽  
GL Semenza
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Cobalt Chloride ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Ferrous Ammonium Sulfate ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Hep3b Cells

Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia- inducible factor 1 (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the EPO gene at a site that is required for transcriptional activation. HIF-1 DNA-binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. DFX appears to induce HIF-1 by chelating iron as induction was inhibited by coadministration of ferrous ammonium sulfate. DFX administration to mice transiently increased EPO RNA levels in the kidney. As previously shown for hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO-producing cells, suggesting the existence of a common hypoxia signal-transduction pathway leading to HIF-1 induction in different cell types.

scholarly journals Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity

2005 ◽  
Vol 65 (19) ◽  
pp. 9047-9055 ◽  
Author(s):  
Dehe Kong ◽  
Eun Jung Park ◽  
Andrew G. Stephen ◽  
Maura Calvani ◽  
John H. Cardellina ◽  
...  
Keyword(s):  
Dna Binding ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Small Molecule Inhibitor ◽  
Binding Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Molecule Inhibitor
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